JPH0999038A - Blood component preserving vessel and vessel connective - Google Patents

Abstract

PROBLEM TO BE SOLVED: To make it possible to suppress the occurrence of hemolysis and microaggregate of preserved blood cell components. SOLUTION: A bag connective is constituted by connecting a blood taking bag 1, a platelet bag 10 and a plasma bag 30 by means of flexible tubes. The blood taking bag 1 used as a bag for preserving the red cells is composed of a soft polyvinyl chloride(PVC) sheet contg. a first plasticizer and a second plasticizer. The first plasticizer, when compounded alone at 32wt.% with the PVC sheet, is soluble in the blood components in such a manner that the elution level of this plasticizer into the blood components is >=15ppm when the prescribed amt. of the blood components are preserved for 35 days at <=4 deg.C in the bag vessel consisting of such PVC sheet. The second plasticizer, when compounded alone at 32wt.% with the PVC sheet, provides >=4.0L/ m<2> .mm.day.atm (30 deg.C) in the oxygen gas permeability of the PVC sheet.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a blood component storage container and a container assembly suitable for storing blood or blood components, particularly erythrocyte-containing liquid.

[0002]

2. Description of the Related Art In recent years, as a container for collecting, separating, and storing blood, a blood component storage container is often formed by stacking sheets made of thermoplastic resin and fusing their peripheral portions to form a bag. It is used.

The characteristics required for this blood component storage container (blood bag) are transparency that allows the state of blood or blood components as a content liquid to be visually recognized, and operations such as blood collection, blood transfusion, and blood component separation to be performed easily. Flexibility (flexibility), strength to withstand these operations, hygiene, safety and the like.

Since soft polyvinyl chloride almost satisfies the above-mentioned required performances, it is currently the mainstream material for blood bags.

By the way, in the field of preservation of red blood cell components,
The development of a dedicated preservation solution has also progressed, and now the erythrocyte component is 4
A storage solution (MAP solution etc.) that can be effectively stored for 2 days has been developed and put into practical use.

[0006] However, while such a preservative solution has made it possible to preserve red blood cell components for a long period of time, a huge aggregate called macroaggregate (hereinafter referred to as MA) is newly generated very frequently after the preservation of red blood cells. The problem of doing is emerging. And, at present, a method for preventing the generation of MA has not been developed.

[0007] Further, in the preservation of red blood cells, it is important to prevent hemolysis thereof (destruction of blood cells). That is, when the hemolysis level of red blood cells increases, the quality of the red blood cell preparation is impaired.

Various methods have been proposed in the past for preventing hemolysis, but all of them are methods for suppressing only hemolysis, and methods for simultaneously suppressing hemolysis and the generation of MA. Has not yet been developed.

[0009]

The object of the present invention is to suppress hemolysis of blood cell components when they are preserved, and
It is an object of the present invention to provide a blood component storage container capable of suppressing the generation of macro aggregates (MA) and excellent in the storage stability of blood components, and a container connected body including the same.

[0010]

The above objects are achieved by the present invention described in (1) to (12) below.

(1) A blood component storage container which is made of a soft polyvinyl chloride sheet containing a first plasticizer and a second plasticizer and stores a liquid containing at least blood cell components. The plasticizer of (3) was added to a polyvinyl chloride sheet alone at 32% by weight, and when a predetermined amount of blood components were stored at 4 ° C for 35 days in a blood component storage container made of the polyvinyl chloride sheet. The plasticizer is soluble in blood components such that the elution level of the plasticizer into the blood components is 15 ppm or more. The second plasticizer alone is blended in a polyvinyl chloride sheet at 32 wt%. When
The oxygen gas permeability of the polyvinyl chloride sheet is 4.0.
A blood component storage container having a L / m ² · mm · day · atm (30 ° C) or higher.

(2) When the second plasticizer alone is blended in a polyvinyl chloride sheet at 32 wt%, a predetermined amount of blood components is added to the blood component storage container made of the polyvinyl chloride sheet. The blood component according to (1) above, wherein the elution level of the plasticizer in the blood component when stored at 35 ° C for 35 days exceeds 2 ppm and is lower than the elution level of the first plasticizer. Storage container.

(3) The second plasticizer is an aliphatic or aromatic ester having at least two ester bonds containing an aliphatic hydrocarbon group having at least 4 carbon atoms in each hydrocarbon chain. The blood component storage container according to (1) or (2).

(4) The second plasticizer is diester phthalate, dialkyl phthalate, adipate ester or dialkyl adipate, each having two or more aliphatic hydrocarbon groups having 4 to 12 carbon atoms. The blood component storage container according to (3).

(5) The blood component storage container according to (4) above, wherein the phthalic acid diester is dinormaldecyl phthalate and the dialkyl adipate is dioctyl adipate.

(6) The first plasticizer has 4 to 4 carbon atoms.
The blood component storage container according to any one of (1) to (5) above, which is an aliphatic or aromatic ester having at least two ester bonds containing 12 hydrocarbon chain aliphatic hydrocarbon groups.

(7) The first plasticizer is a dialkyl phthalate or a dialkyl adipate.
The blood component storage container according to [1].

(8) The blood component storage container according to any one of (1) to (5) above, wherein the first plasticizer is dioctyl phthalate.

(9) The content of the first plasticizer is 5 to 40.
The blood component storage container according to any one of (1) to (8) above, which is wt%.

(10) The content of the second plasticizer is 5 to 45
The blood component storage container according to any one of (1) to (9) above, which is wt%.

(11) The blood component storage container according to any one of (1) to (10) above, wherein the total content of the first plasticizer and the second plasticizer is 20 to 50 wt%.

(12) A container connected body, characterized in that a plurality of containers including at least one blood component storage container according to any one of the above (1) to (11) are connected by a tube.

[0023]

BEST MODE FOR CARRYING OUT THE INVENTION The blood component storage container and container connection body of the present invention will now be described in detail with reference to the preferred embodiments shown in the accompanying drawings.

FIG. 1 is a plan view showing a structural example of a bag connecting body of the present invention. As shown in the figure, the bag connecting body 1
Is a blood collection bag (first bag) 10, a plasma bag (second bag) 20, and a buffy coat bag (third bag).
30) and a drug solution storage bag (fourth bag) 4
It is a quad bag in which 0 and 0 are connected by predetermined tubes.

Blood collection bag 10 located on the left side in FIG.
Is a component of a blood component storage container, and is laminated with polyvinyl chloride flexible sheet materials described later, and is fused (heat fusion, high frequency fusion, etc.) at the peripheral seal portion 12. Alternatively, it has a bag main body 11 which is adhered to form a bag.

A blood storing portion 1 for storing blood to be collected in an inner portion surrounded by the seal portion 12 of the bag body 11.
3 are formed. Further, since the blood collection bag 10 is also used as a red blood cell bag for storing red blood cells, the concentrated red blood cells are finally stored and stored in the blood storage unit 13.

On the upper part of the bag body 11, two opening portions 14, 14 which are openably sealed by peel tabs are formed, and at the side portion of one opening portion 14, other bags 30, 20 are formed. , 40 are formed to connect to the exhaust ports 18. One end of a tube 61 is connected to the discharge port 18 via a connecting member 17. The flow path of the connecting member 17 is closed before breaking, but it is preferable to use a member that opens the flow path when breaking.

The other end of the tube 61 is connected with a bifurcated branch connector 64, and the branch connector 6
4 are connected to one ends of tubes 62 and 63, respectively. A similar branch connector 19 is connected to the other end of the tube 62, and one ends of tubes 25 and 46 are connected to the branch connector, respectively.

Further, one end of a flexible tube 15 is connected to the upper portion of the bag body 11 so as to communicate with the blood component storage portion 13, and the other end of the tube 15 is connected to the other end.
A blood collection needle 152 is attached via a hub 151. In addition, the hub 151 has a cap 1 for enclosing the blood sampling needle 152.
53 is attached.

The plasma bag 20 is formed by stacking flexible sheet materials made of a soft resin such as polyvinyl chloride, which will be described later, and fusion-bonded (heat fusion, high-frequency fusion, etc.) at the peripheral seal portion 22. Alternatively, it has a bag main body 21 that is adhered to form a bag.

A plasma storage portion 23 for storing plasma separated from the blood in the blood collection bag 10 is formed in an inner portion surrounded by the seal portion 22 of the bag body 21.

At the top of the bag body 21, two blood transfusion outlets 2 which are openably sealed by peel tabs are provided.
4 and 24 are formed, and the other end of the tube 25 is connected to the side thereof so as to communicate with the plasma storage unit 23. Thereby, when the flow path of the sealing member 17 is opened, the blood storage part 13 of the blood collection bag 10 and the plasma storage part 23 of the plasma bag 20 are connected by the sealing member 17, the tubes 61, 62,
5 and branch connectors 64 and 19.

The buffy coat bag 30 is formed by stacking flexible sheet materials made of a soft resin such as polyvinyl chloride, which will be described later, at the peripheral seal portion 32.
A bag body 31 is formed by fusing (heat fusing, high-frequency fusing, or the like) or bonding to form a bag.

A buffy coat accommodating portion 33 for accommodating the buffy coat separated from the blood in the blood collecting bag 10 is formed in an inner portion surrounded by the seal portion 32 of the bag body 31.

The other end of the tube 63 is connected to the upper portion of the bag body 31 so as to communicate with the buffy coat storage portion 33.

The chemical solution storage bag 40 is formed by stacking flexible sheet materials made of a soft resin such as polyvinyl chloride, which will be described later, and fusion bonding (heat fusion, high frequency fusion) at the peripheral seal portion 42. Etc.) or is adhered to form a bag body 41.

A chemical liquid storage portion 43 for storing a chemical liquid is formed in an inner portion surrounded by the seal portion 42 of the bag body 41. In the present embodiment, a predetermined amount of red blood cell preservation liquid 47 is stored in the drug solution storage unit 43. Examples of this red blood cell preservation solution include M. A. P. Liquid, S.I. A.
G. M. Liquid, OPTISOL liquid, ADSOL liquid and the like.

At the upper part of the bag body 41, there are two discharge ports 44, 44 which are openably sealed by peel tabs.
Is formed, and the side thereof is provided with the same sealing member 45 that communicates with the chemical liquid storage portion 43. The other end of the tube 46 is connected to the sealing member 45. Thereby, when the flow paths of the sealing members 17 and 45 are opened, the blood storage portion 13 of the blood collection bag 10, the chemical liquid storage portion 43 of the chemical liquid storage bag 40, the plasma storage portion 23 of the plasma bag 20, and the buffy coat bag 30. Of the buffy coat storage portion 33 of the sealing member 17, 45, the tube 6
1, 62, 63, 25, 46 and branch connector 64,
Each communicates with the other via a communication line 19.

It is preferable that the blood collection bag 10 contains an anticoagulant in advance. This anticoagulant
Usually a liquid, for example, ACD-A liquid, CPD liquid, C
Examples thereof include PDA-1 solution and heparin sodium solution.
The amount of these anticoagulants is set to an appropriate amount according to the planned blood collection amount.

In the buffy coat bag 30,
A platelet preservation solution may be previously stored. Examples of the platelet preservation solution include physiological saline, GAC solution, PA
S solution, PSM-1 solution, Synthetic Storage Medium solution and the like.

Next, the conditions and the like of the sheet material constituting each bag 10-40 will be described.

[1] Blood Collection Bag 10 The blood collection bag 10 which is the blood component storage container of the present invention comprises a soft polyvinyl chloride sheet material constituting the blood collection bag 10, and a first plasticizer having a different composition. And a second plasticizer, and suppresses hemolysis by a first plasticizer that is eluted from a sheet material stored in a liquid (hereinafter referred to as a storage liquid) and a second plasticizer that is eluted in a trace amount. The effect (the effect of reducing the amount of hemoglobin leaking into the storage solution) is obtained, and the high gas permeability of the sheet material generated by the second plasticizer causes MA
The excellent blood cell preservability can be obtained by obtaining the effect of suppressing the occurrence of erythrocyte and by exerting these effects in a well-balanced manner.

The resin constituting the sheet material is polyvinyl chloride or a material mainly composed of polyvinyl chloride (for example, a copolymer with a small amount of another polymer material, a polymer blend, a polymer alloy, etc.).

The first plasticizer, when blended alone into a polyvinyl chloride sheet at 32 wt%, stores a predetermined amount of blood components in a blood component storage container made of the polyvinyl chloride sheet at 4 ° C. It is soluble in blood components such that the elution level of the plasticizer into the blood components when stored for a day is 15 ppm or more.

This standard is based on the relationship between the blending ratio of the plasticizer and the elution amount (see FIG. 2) and the relationship between the elution amount and the hemolysis rate described later (see FIG. 3): di-2-ethylhexyl phthalate. (DEHP) was taken as an example and determined from the results of the examination.

Such a first plasticizer has 4 to 1 carbon atoms.
At least 2 containing aliphatic hydrocarbon groups of 2 hydrocarbon chains
An aliphatic or aromatic ester having one ester bond is preferable, and dialkyl phthalate or dialkyl adipate is more preferable.

Specific examples include dioctyl phthalate, dioctyl adipate, di-2-ethylhexyl phthalate, diisonoyl phthalate, isodecyl phthalate, di-2-ethylhexyl maleate, dibutyl phthalate, dihexyl phthalate and the like. These can be used alone or in combination of two or more. In particular, di-2-ethylhexyl phthalate (DEHP) is used because of its stable elution amount and high hemolytic suppression effect.
Or the thing which makes this the main is preferable.

The content of such a first plasticizer in the sheet material is preferably about 5 to 40 wt%,
More preferably about 30 wt%, 10-25 wt%
More preferably, it is about the degree. If it is less than 5 wt%,
The elution amount of the first plasticizer is so small that a sufficient hemolytic suppression effect may not be obtained. On the other hand, if it exceeds 40 wt%, the elution amount becomes excessive, which may affect the physiological activity of blood cells, and the mechanical strength of the bag will be reduced, and the bag will be easily damaged during centrifugation or the like. is there.

On the other hand, when the second plasticizer is blended alone into a polyvinyl chloride sheet at 32 wt%, the polyvinyl chloride sheet has an oxygen gas permeability of 4.0 L / m ² · mm · d
ay · atm (30 ° C) or more, preferably oxygen gas permeability of 4.2 L / m ² · mm · day · atm (30 ° C) or more and carbon dioxide gas permeability of 23.0 L / m ²・ mm ・ day ・ atm (30
℃) or more. In particular, when the second plasticizer alone is blended into a polyvinyl chloride sheet at 32 wt%, a predetermined amount of blood components is placed in a blood component storage container made of the polyvinyl chloride sheet at 4 ° C. for 35 days. When stored, the elution level of the plasticizer in blood components exceeds 2ppm,
Further, it is preferable that it is lower than the elution level of the first plasticizer (fine elution property).

Preferable examples of the second plasticizer having such characteristics are phthalic acid diesters, dialkyl phthalates and adipic acid esters each having two or more aliphatic hydrocarbon groups having 4 to 12 carbon atoms, Dialkyl adipate may be mentioned. In this case, the phthalic acid diester is preferably dinormaldecyl phthalate and the dialkyl adipate is preferably dioctyl adipate.

Particularly, a diester of phthalic acid and an alcohol or an aliphatic hydrocarbon group having 8 to 12 carbon atoms is preferable, and dinormaldecyl phthalate (DnDP) or a main one thereof is more preferable. Further, among dioctyl adipate, di-2-ethylhexyl adipate (DEHA) is more preferable.

The content of the second plasticizer in the sheet material is preferably about 5 to 45 wt%,
More preferably about 30 wt%, 12-30 wt%
More preferably, it is about the degree. If it is less than 5 wt%,
The gas permeability of the sheet material is lowered, and the effect of suppressing the generation of MA is lowered. If it exceeds 45 wt%, the total amount of the first plasticizer and the second plasticizer added is limited (to maintain the mechanical strength of the sheet material). Is reduced and the hemolytic suppression effect is reduced.

The second plasticizer in the present invention has a slight elution property with respect to plasma, and therefore has the following advantages.

When the second plasticizer is non-eluting, only the first plasticizer will be eluted, so a certain amount of the first plasticizer is sufficiently suppressed in order to sufficiently suppress hemolysis. However, in order to maintain the mechanical strength of the sheet material, there is a limit (for example, 50 wt% or less) to the total amount of the first plasticizer and the second plasticizer, as described later. Therefore, the respective addition amounts of the first plasticizer and the second plasticizer are subject to some restrictions.

On the other hand, when the second plasticizer is slightly eluting, the second plasticizer is eluted together with the first plasticizer, so that the first plasticizer having a smaller amount than the above is used. The same hemolytic suppression effect can be obtained with the added amount of the agent, and therefore, the added amount of the second plasticizer can be increased by that amount, so that more excellent gas permeability can be obtained. That is, while maintaining a constant mechanical strength of the sheet material, both the elution amount of the plasticizer and the gas permeability can be improved, and the hemolysis and the generation of MA can be suppressed effectively and in good balance.

The total content of the first plasticizer and the second plasticizer is preferably about 20 to 50 wt%, and 25
More preferably, it is about 40 wt%. If the total content is less than 20 wt%, at least one of the hemolytic suppression effect and MA generation suppression effect may be insufficient, and if it exceeds 50 wt%, the mechanical strength (tensile strength, etc.) of the sheet material When the bag is placed under harsh conditions such as centrifugation, the bag may be damaged.

In addition to the above-mentioned first plasticizer and second plasticizer, various additives such as stabilizers may be added to the sheet material, if necessary. Examples of the stabilizer include various epoxy compounds and compounds of zinc, calcium, barium, and magnesium, and the addition amount thereof in the sheet material is, for example, about 0.1 to 15 wt%.

The thickness of the sheet material is appropriately determined depending on the balance between the mechanical strength required for the sheet material and the gas permeability, but usually 0.2 to 0.5 mm is preferable and 0 0.25 to 0.4 mm is more preferable.

The sheet material as described above can be manufactured, for example, by the following method. Using a kneading machine, the soft polyvinyl chloride and the first and second plasticizers are sufficiently kneaded, and the kneaded product is extruded through a T die or a circular die to obtain a flat sheet-like product or the like. , Thermoforming, blowing, stretching, cutting, and sealing (fusion) of the end portion are sequentially performed to form a desired shape / form.

In order to prevent blocking between the sheets, the surface of the sheet (base material) may be roughened (embossed), or an antiblocking agent, a slip agent, etc. may be added or added.

[2] Platelet Bag The drug solution storage bag 40 can be used as a platelet bag for storing platelets after the red blood cell preservation solution 47 is transferred to the blood storage portion 13 of the blood collection bag 10.

The composition, characteristics, etc. of the sheet material constituting the bag 40 are not particularly limited, and for example, the same material as the sheet material in the blood collection bag 10 can be used. When the same material as the sheet material in the blood collection bag 10 is used, the number of types of sheet material to be prepared is reduced, which is advantageous in manufacturing, and the elution of the plasticizer and the excellent gas permeability can reduce the platelet Storability is improved (for example, effective storage period is 3 to 5 days).

[3] Plasma Bag 20 The composition, characteristics, etc. of the sheet material constituting the plasma bag 20 are as follows.
There is no particular limitation, and the same material as the sheet material in the blood collection bag 10 can be used, for example. When the same material as the sheet material in the blood collection bag 10 is used, the number of types of sheet material to be prepared is reduced, which is advantageous in manufacturing.

[4] Tubes 15, 61, 62, 63,
25, 46 Examples of the constituent material of the tubes 15, 61, 62, 63, 25, 46 include polyvinyl chloride, polyethylene,
Polypropylene, PET, polyester such as PBT, ethylene-vinyl acetate copolymer, polyurethane, polyester elastomer, thermoplastic elastomer such as styrene-butadiene-styrene copolymer, or the like, or materials mainly containing these, Among them, polyvinyl chloride or a material mainly containing polyvinyl chloride is preferable.

If each tube is made of polyvinyl chloride,
Since it has sufficient flexibility and flexibility, it is easy to handle, and is suitable for clogging due to clenching. Furthermore, since the polyvinyl chloride tube has excellent compatibility with the sheet material of the same main bag, when joining these by fusion or adhesion, the joining strength is high and the airtightness is excellent. It is preferable for maintaining durability against centrifugation and sterility. The type and content of the plasticizer used for each tube are not particularly limited.

The container connecting body of the present invention is shown in the drawings as long as it has a blood component storage container for storing a liquid containing a blood cell component, that is, a blood cell storage bag such as the blood collection bag or the red blood cell storage bag described above. Not limited to the configuration,
For example, two consecutive bags consisting of a blood collecting bag and a platelet bag, three consecutive bags consisting of a blood collecting bag, a plasma bag and a platelet bag, four consecutive bags consisting of a blood collecting bag, a platelet bag, a plasma bag and a dedicated red blood cell bag, and red blood cells. Blood collection bag that is also used as a bag, platelet bag,
Any bag may be used, such as a quadruple bag including a plasma bag and a buffy coat bag (small bag for relay), and a bag to which a bag for any purpose is added.

Further, the container connected to the blood component storage container may be a bag made of the materials mentioned above as the constituent material of the tube or a container of other form.

[0068]

EXAMPLES Specific examples of the present invention will be described below.

(Examples 1 and 2, Comparative Examples 1 to 4)

A. experimental method

<1> Manufacture of a connected bag A sheet having the composition and characteristics shown in Table 1 below was laminated, cut, and its peripheral portion was heat-sealed to manufacture a blood collection bag. Similarly, a platelet bag (medical solution storage bag), a plasma bag and a buffy coat bag were manufactured.

A red blood cell preservation solution (MAP solution / sodium chloride: 5.52 g / l, adenine: 0.16 g / l, glucose: 8.01) was passed through a tube in a platelet bag (medical solution storage bag).
g / l, mannitol: 16.19 g / l, citric acid: 0.22 g /
l, sodium citrate: 1.67 g / l, sodium phosphate:
95 ml of an aqueous solution containing 1.04 g / l) was dispensed, each bag was connected with a flexible tube, and a blood collection tube was connected to the blood collection bag, and an anticoagulant (ACD-A solution / quenching) was connected through the tube. Aqueous solution containing sodium acidate: 22.0 g / l, citric acid: 8.0 g / l, glucose: 22.0 g / l) 6
0 ml was dispensed to produce a quad bag assembly.

Next, the bag connected body was subjected to high-pressure steam sterilization (121 ° C., 30 min). The constitution of each bag in the bag connecting body is shown in Table 2 below.

The tubes connecting the bags and the blood collection tubes were made of soft polyvinyl chloride containing di-2-ethylhexyl phthalate: 36.7 wt%.

[0075]

[Table 1]

[0076]

[Table 2]

<2> Heavy Metal and Eluted Substance Test Heavy metals and eluted substances were tested in accordance with the standard (Japanese Pharmacopoeia General Test Method “Plastic Container Test Method for Infusion”).

<3> Separation of blood components About 400 ml of whole blood was placed in a blood collection bag, and the bag connected body was centrifuged by a centrifuge, and three components of platelet-poor plasma, buffy coat and concentrated red blood cells from the upper layer. Separated.

Next, the platelet poor plasma in the blood collection bag was transferred to the plasma bag via the tube, and then the buffy coat was transferred to the buffy coat bag via the tube to leave concentrated red blood cells in the blood collection bag.

Next, the erythrocyte preservation solution previously placed in the platelet bag was transferred to the blood collection bag through the tube, and then the predetermined tube was sealed with a heat seal and cut to add the erythrocyte preservation solution. It was separated into a blood collection bag containing concentrated red blood cells (red blood cell bag), a plasma bag containing platelet poor plasma, and a two-bag connected body including a buffy coat bag containing buffy coat and a platelet bag.

The buffy coat in the buffy coat bag is separated into concentrated platelets in the upper layer and white blood cells in the lower layer by gently centrifuging the two-bag connected body.
The platelet concentrate was transferred to the platelet bag via the tube.

Finally, the tube connecting the platelet bag and the buffy coat bag was sealed and cut to separate them.

<4> Confirmation of MA Occurrence State The blood collection bag containing concentrated red blood cells containing red blood cell preservation solution obtained in <3> above was stored at 4 ° C. for 35 days, and each of Example 1 and Comparative Examples 1 to 3 was examined. The state of MA generation was observed (results are shown in Table 3).

<5> Confirmation of hemolysis level The blood collection bag containing concentrated red blood cells containing red blood cell preservation solution obtained in the above <3> was stored at 4 ° C for 35 days, and for each of Example 1 and Comparative Examples 1 to 3, The stored solution was aseptically sampled by 1 ml, and the hemoglobin concentration and hematocrit value in the sample solution taken out were measured by an automatic hemocytometer (Sysmex CC-180 manufactured by Toa Medical Electronics Co., Ltd.).

A portion of the sample liquid taken out was put into a centrifuge (KR-702 manufactured by Kubota Manufacturing Co., Ltd.) at 1500
G was centrifuged for 10 minutes, the supernatant plasma was collected, and the hemoglobin concentration in the plasma was measured by the leuco crystal violet method (LCV method).

The measured values obtained as described above were substituted into the following equation to calculate the hemolysis rate (results are shown in Table 3).

[0087]

[Equation 1]

<6> Confirmation of Platelet Preservation The platelet bag containing the concentrated platelets obtained in <3> was stored by shaking at 22 ° C., and 1 ml of the content solution was aseptically prepared on each of days 0, 3, and 5. The number of platelets in the sample liquid sampled and taken out was measured by the automatic hemocytometer (results are shown in Table 4).

The pH value of the sample liquid taken out (at3
Blood gas / pH measuring device (Instrumentation Lab.
Manufactured by IL 1304) (results are shown in Table 5).

<7> Centrifugation Experiment A predetermined amount of distilled water was placed in a blood collection bag, and centrifugation was performed under the following conditions.

Centrifuge: Hitachi, Ltd., himac CR7B3 Conditions: 1.80 × 10 ⁸ g · sec, 4000 rpm (4.6
70G), 22 ° C

After centrifugation, the blood collection bag was taken out from the auxiliary cup and examined for damage (results are shown in Table 6).

B. Experimental result

<1> Manufacture of Sheets and Bags Manufacture (adjustment) of sheets and the like was all smoothly performed, and a sheet having a high degree of uniformity was obtained. In addition, the production of each bag was similarly smoothly performed.

<2> Results of Heavy Metal and Eluate Tests: In all the examples, it was confirmed that the heavy metals and eluate also cleared the standard (Japanese Pharmacopoeia General Test Method "Plastic Container Test for Infusion Solution").

<3> Evaluation results of erythrocyte preservability Table 3 below shows the occurrence of macroaggregates (MA) and the level of hemolysis. As shown in Table 3, it was confirmed that the blood collection bags of Examples 1 and 2 did not generate MA and had a low hemolysis level.

[0097]

[Table 3]

<4> Evaluation Results of Platelet Preservability Table 4 below shows changes in the number of platelets with time, and Table 5 below shows changes with time of pH value. As shown in Table 4, there is almost no change in the platelet count in each case. Thus, under the condition that the number of platelets is almost the same, as shown in Table 5, in Comparative Example 2, a decrease in pH value that is considered to be due to its low gas permeability, that is, a decrease in platelet quality. However, it was confirmed that the others could be stored almost stably up to 5 days.

[0099]

[Table 4]

[0100]

[Table 5]

<5> Results of Evaluation of Bag Strength by Centrifuge Experiment Table 6 below shows the number of breakage occurrences of the blood collection bags used in the centrifuge experiment. The blood collection bags of Examples 1 and 2 are both
It was confirmed that the glass did not break and had a strength sufficient to withstand the centrifugation operation.

[0102]

[Table 6]

[0103]

As described above, according to the blood component storage container and the container connected body of the present invention, the hemolysis of the blood cell component when the blood cell component is stored due to the moderate elution of the plasticizer and the high gas permeability. And the action of suppressing the generation of macro aggregates (MA), and both of these actions are excellent.

In particular, when a slightly eluting agent is used as the second plasticizer, the first plasticizer and the second plasticizer are
When a predetermined more preferable composition is used, when the content of the first plasticizer, the content of the second plasticizer, or the total amount thereof is set within the predetermined range described above, blood The above effect is more remarkably exhibited while ensuring a sufficient mechanical strength in the component storage container, particularly, a strength capable of withstanding a centrifugal separation operation. For this reason, it becomes possible to store red blood cells and the like in high quality for a long period of time.

Further, the blood component storage container and the connected container of the present invention are easy to handle, easy to manufacture, and excellent in safety.

[Brief description of drawings]

FIG. 1 is a plan view showing a configuration example of a container connected body of the present invention.

FIG. 2 is a graph showing the relationship between the compounding ratio of a plasticizer (DEHP) and the elution amount.

FIG. 3 is a graph showing the relationship between the elution amount of a plasticizer (DEHP) and the hemolysis rate.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 bag connection body 10 blood collection bag 11 bag body 12 seal part 13 blood storage part 14 discharge port 15 tube 151 hub 152 blood collection needle 153 cap 17 sealing member 18 discharge port 19 branch connector 20 plasma bag 21 bag body 22 seal part 23 plasma Storage part 24 Discharge port 25 Tube 30 Buffy coat bag 31 Bag body 32 Seal part 33 Buffy coat storage part 40 Drug solution storage bag (platelet bag) 41 Bag body 42 Seal part 43 Chemical solution storage part 44 Discharge port 45 Sealing member 46 Tube 47 Red blood cell preservation solution 61, 62, 63 tube 64 branch connector

Claims (12)

[Claims] 1. A blood component storage container which is made of a soft polyvinyl chloride sheet containing a first plasticizer and a second plasticizer and stores a liquid containing at least blood cell components, said first component comprising: When 32% by weight of a plasticizer is added alone to a polyvinyl chloride sheet, a predetermined amount of blood components is stored in a blood component storage container made of the polyvinyl chloride sheet at 4 ° C.
The plasticizer is soluble in blood components such that the elution level of the plasticizer into the blood components is 15 ppm or more when stored for 35 days below, and the second plasticizer is polyvinyl chloride. Oxygen gas permeability of the polyvinyl chloride sheet is 4.0 L / m ² · mm · day · atm (30 ℃) when it is blended alone into the sheet.
A blood component storage container characterized by the above. 2. The second plasticizer, when added alone to a polyvinyl chloride sheet at 32 wt%, stores a predetermined amount of blood components at 4 ° C. in a blood component storage container made of the polyvinyl chloride sheet. When the plasticizer was stored for 35 days below, the elution level of the plasticizer into blood components exceeded 2 ppm, and
The blood component storage container according to claim 1, which has a lower elution level than that of the plasticizer. 3. The second plasticizer is an aliphatic or aromatic ester having at least two ester bonds including an aliphatic hydrocarbon group having at least 4 carbon atoms in each hydrocarbon chain. The blood component storage container according to 1 or 2. 4. The second plasticizer has a carbon number of 4 respectively.
The blood component storage container according to claim 3, which is a phthalic acid diester, a dialkyl phthalate, an adipate ester, or a dialkyl adipate having two or more aliphatic hydrocarbon groups of 1 to 12. 5. The blood component storage container according to claim 4, wherein the phthalic acid diester is dinormaldecyl phthalate and the dialkyl adipate is dioctyl adipate. 6. The first plasticizer is an aliphatic or aromatic ester having at least two ester bonds containing an aliphatic hydrocarbon group having a hydrocarbon chain of 4 to 12 carbon atoms. The blood component storage container according to any one of 1. 7. The blood component storage container according to claim 6, wherein the first plasticizer is dialkyl phthalate or dialkyl adipate. 8. The blood component storage container according to claim 1, wherein the first plasticizer is dioctyl phthalate. 9. The blood component storage container according to claim 1, wherein the content of the first plasticizer is 5 to 40 wt%. 10. The content of the second plasticizer is 5 to 45 wt%.
The blood component storage container according to any one of claims 1 to 9, which is 11. The total content of the first plasticizer and the second plasticizer is 20 to 50% by weight.
The blood component storage container according to any one of 1. 12. A container connected body, which is formed by connecting a plurality of containers including at least one blood component storage container according to claim 1 with a tube.